The Role of Atypical Antipsychotic Therapy for Patients with Treatment- Resistant Bipolar Depression

f Ps al o ych rn ia u tr o y J

Journal of Psychiatry Shah, J Psychiatry 2014, 17:6 ISSN: 2378-5756 DOI:10.4172/2378-5756.1000150

Review Article Open Access The Role of Atypical Antipsychotic Therapy for Patients with Treatment- Resistant Bipolar Depression

Anish S Shah* 1260 N Dutton Ave, Suite 275, Santa Rosa, CA, 95401, USA

*Corresponding author: Anish S. Shah, 1260 N Dutton Ave, Suite 275, Santa Rosa, Ca, 95401, USA, Tel: 7076968045; E-mail: [email protected]

Received Date: August 29, 2014, Accepted Date: September 23, 2014, Published Date: September 30, 2014 Copyright: © 2014, Anish S. Shah et al., This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Physicians treating patients with bipolar depression have a unique challenge when considering drug therapy. Historically, patients with bipolar depression have been treated with SSRIs or other medications commonly utilized with patients presenting with non-bipolar depression. Indeed, many of these medications are not ideal for patients suffering from bipolar depression. Recently, a class of second-generation atypical antipsychotics has emerged as an exciting new avenue for the treatment of bipolar depressive episodes. While these medications have received a wealth of empirical support for treating treatment-resistant unipolar depression, less is known about the efficacy of these medications in treating bipolar depression. Early evidence is promising, though additional trials may be warranted to more clearly delineate the role of second-generation atypical antipsychotics in treating bipolar depressive episodes. This article discusses the second-generation atypical antipsychotics that have received empirical support for use in treating depressive symptoms in patients with bipolar depression. Current FDA approvals for usage are reviewed and avenues for future work are proposed.

Keywords: Bipolar depression; Treatment-resistant; Depression; Individuals with bipolar depression present unique challenges for Second-generation antipsychotics; Atypical antipsychotic therapy; their treating physicians. In fact, depression that is induced by bipolar Depression treatment disorder is regarded as more refractory than unipolar depression and is characterized by a less favorable treatment response [7]. Introduction Traditionally, in the US, individuals with depression that has been induced by bipolar disorder are treated with mediations that are The annual prevalence estimates for bipolar disorder around the known to be effective for individuals suffering from unipolar world range from 0.0% in some countries to 0.6%, and are around depression; however, controversy exists. Indeed, as a general principal, 0.3% for bipolar II disorder [1]. For both bipolar disorders, the mean Canadian physicians are encouraged to discontinue antidepressants age of onset for the first major depressive episode is between with their patients who have bipolar depressive episodes [9]. These approximately 18 to 20 years old, with bipolar II having a slightly later medications, traditionally used for unipolar depression, include onset. Suicide risk is particularly important among individuals with selective serotonin reuptake inhibitors (SSRIs), serotonin- bipolar disorder. In fact, some estimates have suggested that the risk norepinephrine reuptake inhibitors (SNRIs), and bupropion. Indeed, a for suicide among individuals with bipolar disorder is more than 15 meta-analysis, which considered evidence from twelve randomized, times more than that of the general population [2]. Moreover, bipolar controlled trials, found some support for the efficacy of disorder is associated with significant functional impairments. antidepressants as a short-term management option for bipolar Approximately 30% of individuals with bipolar disorder exhibit depression [9]. However, physicians considering these medications to significant impairment at work [3]. Individuals with bipolar disorder treat depressive episodes among their patients with bipolar disorder are more likely to fall in the lower socioeconomic classes, perform have done so with particular caution, as these medications have been worse on tests of cognitive abilities, and endure interpersonal shown to precipitate accelerated mood switching to mania or even difficulties [3-5]. While acute manic episodes associated with bipolar activate rapid cycling [10,11]. This risk appears to be particularly disorder have the potential to be dangerous, patients with bipolar relevant for the use of SNRIs. Evidence from clinical trials using these disorder also tend to suffer more from episodes of depression for medications have indicated that a generous portion of bipolar disorder longer periods of time [6,7]. Thus, it is believed that it is actually the patients can expect a degree of improvement in their depressive depressive episodes associated with bipolar disorder that account for symptoms from these treatments when compared to a placebo- the individual’s persistent functional impairment [8]. Indeed, findings controlled group (i.e., approximately 45% achieved remission status) from previous studies have suggested that individuals recently [13]. diagnosed with bipolar disorder spend approximately three times more time in a depressive episode compared to both mania and Nonetheless, concerns with regard to the divide between statistically hypomania [9]. Further, depressive episodes associated with bipolar significant and subjectively significant improvements still exist. More disorder carry with the man augmented risk for relapse into mania, specifically, patients are considered treatment “responders” simply by along with poorer prognoses for the patient [9]. achieving a 50% improvement in depressive symptoms according to a standardized rating scale. While this, indeed, characterizes a statistically significant improvement in symptom presentation in

J Psychiatry Volume 17 • Issue 6 • Psychiatry-14-126 Journal of Psychiatry, an Open Access Citation: Shah SA (2014) The Role of Atypical Antipsychotic Therapy for Patients with Treatment-Resistant Bipolar Depression. J Psychiatry 17: 1000150. doi:10.4172/2378-5756.1000150

Page 2 of 4 terms of the rating scale, a portion of these patients may continue to results are somewhat mixed. Indeed, several studies have found that suffer from clinically concerning symptoms. Further, some patients while aripiprazole was associated with improvements in patient- may even continue to exhibit functional impairments from the reported symptoms of depression in the early phases of treatment; refractory symptoms of depression. This subset of patients however, when symptom improvement was compared after 8 weeks, characterized by treatment-resistant bipolar depression warranted a aripiprazole did not significantly differ from placebo [33]. search for alternative treatment options, which led to the use of Furthermore, while aripiprazole has been supported as effective in antipsychotics. Currently, several drugs have received FDA approval delaying the relapse of manic episodes in patients with bipolar for the maintenance of bipolar disorder, including mood stabilizers, disorder, little evidence exists for its use in delaying the onset of such as lamotrigine and lithium, and atypical antipsychotics, such as depressive episodes. Findings from current research have shown that olanzapine, aripiprazole, and risperidone. However, this subclass of relapse rates for bipolar depression are similar for aripiprazole and antipsychotics, in particular, has been shown to lengthen the time placebo [33]. Indeed, the data remain mixed for the efficacy of between episodes of depressive symptoms [11]. These medications aripiprazole in treating bipolar depression, which may be due to a have been particularly promising in trials on adults who present with number of study limitations, including rapid titration and the use of extensive histories of drug trials for treating their bipolar depressive high dosages. More work is necessary to examine the role of episodes. Indeed, there is currently more support for the use of aripiprazole in treating bipolar disorder. atypical antipsychotics among populations of unipolar depression; Risperidone has received FDA approval for treating schizophrenia however, several recent trials have suggested that the augmentation of in adults and adolescents, bipolar disorder (both manic and mixed atypical antipsychotics may be equally effective for treating bipolar episodes), bipolar mania in adults, child, and adolescents, major depression [14-23]. depressive disorder, and treatment-refractory depressive disorder Clinical trials regarding atypical antipsychotic therapy for bipolar [34-37]. Findings from previous studies have supported the use of depression were thoroughly reviewed for the purpose of this article. risperidone in the treatment of unipolar depression, particularly in The literature search focused on FDA-approved, second generation instances where the patient has not responded to SSRIs alone [36-38]. antipsychotics for bipolar disorder and bipolar depression. Few recent studies exist examining the efficacy of risperidone in the Accordingly, this article provides a discussion of the use of second- treatment of bipolar depression and the findings from these studies generation, atypical antipsychotics as an augmentation treatment for remain mixed. While some data has shown that risperidone is patients with bipolar depression, particularly those with refractory associated with improvements in patient-reported symptoms of depressive symptoms. bipolar depression [34], other findings have suggested that these improvements do not significantly differ from placebo [35]. Indeed, FDA Approval of Second-Generation Antipsychotics more data is necessary to examine the use of risperidone in treating bipolar depression. Olanzapine has received FDA approval for treating schizophrenia in adults and adolescents, bipolar I disorderin adults and adolescents Ziprasidone has received FDA approval for treating schizophrenia (mixed or manic bipolar episodes), in combination with fluoxetine for in adults, bipolar I disorder in adults (both manic and mixed episodes), the treatment of bipolar I depression in adults, children, and and maintenance of bipolar I disorder in adults [39,40]. Findings from adolescents, and for treatment-resistant depression in adults [24,25]. previous studies have supported the use of ziprasidone in the treatment Several previous studies have documented olanzapine as beneficial for of unipolar depression, particularly in instances where the patient has treating patients with treatment-resistant depression [24-28]. not responded to SSRIs alone [39]. Very little data exists on the use of ziprasidone in treating bipolar depression. While some evidence exists Quetiapine has received FDA approval for treating schizophrenia in on the benefits of ziprasidone in reducing patient-reported symptoms adults and adolescents aged 13 to 17, bipolar mania in adults, children, of bipolar depression, these findings have not been compared to and adolescents aged 10-17 years, bipolar depression, and for bipolar placebo [40]. Thus, future work is necessary to compare the reduction maintenance [29-31]. Further, the immediate release form of in depressive symptoms among patients with bipolar disorder across quetiapine (i.e., quetiapine IR) has not received FDA approval for the trials of ziprasidone and placebo. Further, studies are also necessary to treatment of depression; however, the extended release form (i.e., examine the long-term benefits of ziprasidone in preventing the relapse quetiapine XR) is supported by the FDA as an adjunctive treatment for of depressive episodes among patients with bipolar disorder. major depressive disorder. Existing work has supported quetiapine as an augment agent in the treatment of treatment-resistant depression [29-31]. Additionally, a recently-conducted study examined the pooled Two recently developed antipsychotics (asenapine and Lurasidone) data of four placebo-controlled trials on the use of quetiapine for the have received FDA approval for the treatment of schizophrenia and treatment of bipolar II depression. This study found that quetiapine bipolar disorder [41,42]. Findings from clinical trials have supported was associated with higher rates of remission and greater Lurasidone’s efficacy in treating bipolar depression as both a improvements in patient-reported depressive symptoms when monotherapy, as well as an adjunctive therapy, and these benefits have compared to placebo [31]. been found to be superior to placebo [41,42]. Outcomes from clinical trials specifically examining the efficacy of asenapine on the treatment Aripiprazole has received FDA approval for treating schizophrenia of depression associated with bipolar disorder have not yet been in adults and adolescents, bipolar disorder (both manic and mixed published. episodes), bipolar mania in adults, children, and adolescents, bipolar I maintenance, and major depressive disorder [32,33]. Several studies Conclusion and Future Directions exist, which have documented the beneficial effects of using aripiprazole as an augment medication for treating patients with Bipolar depression is of particular concern when considering drug treatment-resistant depression [32,33]. In terms of bipolar depression, therapy, as there is some risk for inducing mania or rapid cycling.

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